Contact lenses with hydrophilic crosslinkers

ABSTRACT

Hydrophilic contact lenses made using a crosslinking agent of the formula 
     
         A--X--(O--(C(O).sub.i --R--(C(O)).sub.i --O--X).sub.n -A 
    
     wherein R contains one or more cyclic or bicyclic moiety, X is linear or branched alkyl or alkenyl, optionally substituted, and A is acrylate, methacrylate, vinylbenzoyloxy or vinylphenoxy, exhibit superior hydrophilicity, oxygen transmissivity, and physical properties.

FIELD OF THE INVENTION

The present invention relates to contact lenses made from hydrophilicpolymeric material. Such contact lenses, also known often as "soft"contact lenses, are notably comfortable and permit diffusion of waterand oxygen therethrough to the cornea.

Hydrophilic polymers used to produce contact lenses are typicallyhomopolymers or copolymers of one or more often more than one monomer.In order to attain structural integrity and strength, the polymer iscrosslinked with a small but effective amount of one or morecrosslinking agents. Such agents are typically reactive at two differentsites, and thereby covalently bond into two different polymer chains andform a stable three-dimensional network.

Crosslinking agents conventionally used in the production of hydrophiliccontact lenses, such as ethylene glycol dimethacrylate and diglycidylbisphenol A dimethacrylate, have been known to exhibit an undesirabletendency to reduce the water content of the lens with increasing contentof the crosslinking agent in the lens polymer. This characteristiccauses the operator to choose between higher water content (andassociated comfort and enhancement of corneal health) and lens strength.

There accordingly remains a need in this field for new polymers for usein producing contact lenses, which provide higher levels of both watercontent and structural integrity.

DESCRIPTION OF PRIOR ART

U.S. Pat. No. 3,980,483 to Nishikubo et al. discloses photocurablecompositions useful in making relief images on a substrate, wherein thecompositions contain the reaction product of the addition compoundobtained from an epoxy resin and a photopolymerizable α,β-unsaturatedcarboxylic acid, and a dibasic acid anhydride; a photopolymerizablemonomer; and an initiator. Similar disclosures are found in U.S. Pat.No. 4,146,452 to Weber et al., U.S. Pat. No. 4,072,592 to Due et al.,and U.S. Pat. No. 4,284,710 to Burg et al. These disclosures do not atall address the production of contact lenses, nor the problemsassociated with obtaining a desirable balance of properties in ahydrophilic contact lens.

BRIEF SUMMARY OF THE INVENTION

The present invention satisfies the needs described hereinabove andprovides the additional advantages disclosed herein. One aspect of theinvention is a hydrophilic contact lens formed by copolymerizing apolymerizable mixture comprising at least one hydrophilic monomer andfurther comprising at least one crosslinking agent of the generalformula (1)

    A--X--(O--(C(O)).sub.i --R--(C(O)).sub.i --O--X).sub.n --A (1)

wherein n is 1 to 6; each i is independently 0 or 1;

R is a divalent bridge containing at least one saturated or unsaturatedcyclic or bicyclic moiety;

X is a linear divalent alkyl bridge containing 2 to 12 carbon atomsoptionally substituted with at least one side chain which contains a--OC(O)-- linkage and a total of up to 12 carbon atoms, which isoptionally substituted with fluorine, and which optionally contains aphenyl ring that can optionally be substituted with alkyl containing 1to 6 carbon atoms; and

A is acrylate, methacrylate, vinylbenzoyloxy, or vinyl-phenoxy, and isoptionally endcapped with a polyalkoxy group containing up to 10 ethoxyor propoxy units;

provided that one or both of R and X is substituted with at least one--COOH group.

Another aspect of the present invention is the method of producing acontact lens which comprises forming a polymerizable mixture which uponpolymerization forms a hydrophilic polymer, the mixture containing atleast one crosslinking agent of formula (1) defined herein, andpolymerizing the mixture in the shape of a contact lens.

DETAILED DESCRIPTION OF THE INVENTION

The contact lenses of the present invention can be made bycopolymerizing a mixture containing one or more monomers including atleast one monomer ("hydrophilic monomer") which imparts hydrophilicityto the polymerized lens, and also including at least one crosslinkingagent which imparts structural integrity to the lens, and alsopreferably including a polymerization initiator. A lens is considered"hydrophilic" if it is capable from its dry state of absorbing water (oran aqueous saline solution) and of holding the absorbed water inequilibrium.

Suitable hydrophilic monomers are preferably esters of carboxylic acidsthat contain ethylenic unsaturation, such as acrylic, methacrylic,fumaric and maleic acids. Preferred esters includemonohydroxy-substituted and dihydroxy-substituted alkyl, alkoxyalkyl,and poly(alkoxy) esters of such acids. More preferred are esters ofacrylic and methacrylic acid with alkyl groups (preferably containing 1to 6 carbon atoms) wherein the alkyl group is substituted with 1, 2 ormore hydroxyl groups. Examples of such hydroxy esters include2-hydroxyethyl methacrylate ("HEMA"), 2-hydroxyethyl acrylate ("HEA"),2,3-dihydroxypropyl methacrylate and acrylate, and monohydroxypropylacrylate and methacrylate.

Other useful monomers (comonomers) include ethylenically unsaturatedcarboxylic acids per se, such as acrylic acid, methacrylic acid, fumaricacid and maleic acid; heterocyclic N-vinyl lactams such as N-vinylpyrrolidone; noncyclic amides such asN-(1,1-dimethyl-3-oxobutyl)-acrylamide; aminoalkyl esters ofethylenically unsaturated acids, such as 2-aminoethyl methacrylate andthe like; mercaptoalkyl esters of ethylenically unsaturated acids;perfluoroalkyl methacrylates and acrylates, especially those containing1 to 6 carbon atoms; methacrylic anhydride; and acrylic anhydride.

The foregoing monomers generally comprise 60-98 wt. % of thepolymerizable components of the polymerizable mixture, and preferablyabout 65-95 wt. % thereof.

The crosslinking agent(s) will comprise a difunctional or polyfunctionalcomonomer having 2 or more sites that react with the other monomericspecies present. Typically these sites contain polymerizable ethylenicunsaturation. Examples of conventional compounds of this type useful inproducing contact lenses include ethylene glycol dimethacrylate andtrimethylolpropane trimethacrylate. Other useful crosslinking agentsinclude polyethylene glycol of molecular weight 100 to about 8,000,di-endcapped with acrylate or methacrylate; diglycidyl bisphenol A dioldi-endcapped with acrylate or methacrylate; and bisphenol A di-endcappedwith acrylate or methacrylate.

An essential aspect of the present invention is the incorporation in thepolymerizable mixture of at least one crosslinking agent of the formula(1)

    A--X--(O--(C(O)).sub.i --R--(C(O)).sub.i --O--X).sub.n --A (1)

In formula (1), the subscript n is 1 to 6, meaning that the crosslinkingagent can be based on an oligomeric epoxy resin containing repeating Rand X units (as defined herein) and endcapped with units A as definedherein. Preferably, n is 1 or 2 and more preferably n is 1.

The subscript i is independently in each occurrence 0 or 1, meaning thateach R is linked into the molecule through ester or oxy linkages. Forease of synthesis as will be described more fully herein, it ispreferred that when i is 1, the R component carries at least one andmore preferably two --COOH substituents, and when i is 0, the Acomponent carries at least 1 and more preferably two --COOHsubstituents.

The divalent component R in formula (1) contains one or more than onering; when more than one ring is present they can be fused to eachother, connected to each other by a chemical bond, or both connected toan intervening segment.

One preferred structure for R is --Ph--Z--Ph-- wherein Ph denotes aphenyl ring, and Z is a divalent segment connecting the two Ph rings.Each Ph ring can be unsubstituted or, optionally, can be substitutedwith one or two alkyl groups containing 1 to 6 carbon atoms. Preferably,Z is a chemical bond, --O--, --SO₂ --, or --C(Y)₂ --, wherein Y ishydrogen or alkyl containing 1 to 6 carbon atoms which is optionallyfluorinated. Preferred examples of Y are hydrogen, methyl, andtrifluoromethyl.

Another preferred structure for R is a phenyl ring --Ph-- which canoptionally be unsubstituted or substituted as set forth above. R canalso be any fused two-ring homocyclic moiety, such as naphthyl,dihydronaphthyl, tetrahydro-hydronaphthyl, indanyl, indenyl, orbicyclics such as bicyclo [2.2.2] oct-7-ene (which, if drawn, wouldcomprise a cyclohexane ring having an ethylenic bridge --CH═CH--connecting the two carbons of the cyclohexane situated para to eachother). In addition, R can take the form of a moiety --Z-- between twoof the foregoing fused two-ring homocyclic moieties. The fused two-ringmoieties can be unsubstituted or, as with the Ph, can optionally besubstituted with alkyl containing 1 to 6 carbon atoms which isoptionally fluorinated.

As will be stated at several points herein, the component R is alsooptionally substituted with one, two or more --COOH groups.

Referring again to formula (1), the component X comprises a divalentlinear alkyl group which contains 2 to 12 carbon atoms. X optionally issubstituted with at least one side chain alkyl or alkenyl segment whichcontains a --OC(O)-- linkage. The optional side chain segment contains atotal of up to 12 carbon atoms and can optionally be substituted withfluorine at some or all substitutional sites. The optional side chainsegment can include a phenyl ring, which itself can optionally besubstituted with alkyl containing 1 to 6 carbon atoms. Such side chainscan be branched, and alkenyl side chains can contain a carbon-carbondouble bond in the side chain and in a branch therefrom, for instance as═CH₂.

In preferred embodiments, X includes 2 to 6 and more preferably 2 to 3carbon atoms in the main chain of the molecule depicted in formula (1),with the remaining portion of X, if any, as a side chain. Examples ofpreferred side chains include --OC(O)-- to which is attached --CH₂ CH₂--, --CH(CH₃)CH₂ --, --CH═CH--, --CF₂ CF₂ --, --CF₂ CF₂ CF₂, --CH₂ CH₂CH₂, --CH(═CH₂)CH₂ --, and --C₆ H₄ --, capped with --H and optionallysubstituted with one, two or more --COOH groups. Preferably, when X issubstituted with --COOH, the --COOH is attached at the end of a sidechain pendant from the portion of X that lies in the main chain betweenR and A.

The component A in formula (1) is preferably an acrylate or methacrylateendcapping unit but can also be vinylbenzoyloxy (i.e., derived fromvinyl benzoic acid such as 4-vinyl benzoic acid) or vinyl phenoxy (i.e.,derived from vinylphenol). Optionally, a polyethoxy or polypropoxysegment containing up to 20 ethoxy or propoxy units, is present betweena and the X segment.

Compounds of formula (1) can be synthesized by several differentpathways. As will be seen, the choice of pathway is determined somewhatby the desired point of attachment of the 1 or more --COOH groups. Inone pathway, a precursor of the compound of formula (1) is formedwherein in at least two occurrences a component X' appears instead of X,wherein X' contains at least one pendant hydroxyl group. This can beachieved by reacting a diol or diacid of R, of the formula HO--R--OH orHOOC--R--COOH, as the case may be, to form the correspondingdihydroxyalkyl-endcapped intermediate which is then diesterified withacrylic acid, methacrylic acid, or a polyethoxylated derivative thereof.

Next, the remaining pendant hydroxy groups are reacted with a cyclicacid anhydride such that the anhydride opens, esterifies the pendanthydroxy groups, and creates the desired branched structure of X which isconnected to the main chain of the crosslinking agent through a--OC(O)-- linkage and is terminated with a --COOH group. Suitableanhydrides include succinic, methyl succinic, maleic, itaconic,glutaric, perfluoroglutaric, perfluorosuccinic, and phthalic anhydrides.The reaction with the anhydride is carried out in any inert aproticsolvent, such as methylene chloride, acetonitrile, toluene, pyridine,isopropyl acetate, or tetrahydrofuran. The reaction is preferablycarried out in the presence of a small but effective amount of acatalyst such as 4-dimethylamino pyridine and triethylamine. This firstsynthetic pathway is especially adaptable to reactions of bisphenoldiols, thereby forming compounds of formula (1) wherein R is--Ph--Z--Ph-- and the required one or more --COOH groups depend from theX component. Here, typically, there are two or more such --COOHsubstituents.

A second synthetic pathway begins with a dianhydride of the component Rand reacts it with 2 molar equivalents of a hydroxy-terminated compoundof the formula HO--X--A. This reaction is carried in a suitable aproticsolvent such as any of the foregoing solvents disclosed above as usefulin the reaction with the anhydride in the first synthetic pathway. Amongthe useful dianhydrides in this reaction are 4,4-(hexafluoroisopropylidene) di-phthalic anhydride, 4, 4'-oxydiphthalicanhydride, 4, 4'-biphthalic anhydride, 3, 3 ', 4, 4 '-diphenylsulfonetetracarboxylic dianhydride, bicyclo [2.2.2] oct-7-ene-2,3, 5, 6 -tetracarboxylic dianhydride, 1,2,4,5-benzene tetracarboxylicdianhydride, and 1,4,5,8-naphthalene tetracarboxylic dianhydride. Thissynthetic pathway is especially adaptable to producing compounds offormula (1) wherein one or more and more typically two or more --COOHgroups required are pendant from the R component.

In either case, or following other synthetic routes to the same endwhich may be apparent, the desired compound of formula (1) is recoveredand added to the monomer mixture described above. The amount of allcrosslinking agents present should be about 5 to about 30 wt. % of allpolymerizable components present. Preferably, the crosslinking agent offormula (1) comprises at least about 0.1 wt. % of all polymerizablecomponents present, up to about 30 wt. % thereof, depending upon whetherother crosslinking agents are present as well.

The reaction mixture also should include an initiator, usually in anamount from about 0.05 to about 5.0 percent by weight of thepolymerizable components of the mixture. Any of numerous well-knowninitiators can be used, presenting a variety of initiation mechanisms.For instance, polymerization can be initiated thermally, or by exposureof the mixture to ultraviolet light, an electron beam, or otherradiation. Examples of useful initiators include lauroyl peroxide,benzoyl peroxide, isopropyl percarbonate, azobisisobutyronitrile, redoxsystems such as the ammonium persulfate/sodium metabisulfite system, andbenzoin and its ethers. The preferred initiation mechanism isultraviolet radiation ("UV"), and the preferred UV initiator isalpha-hydroxy-alpha, alpha-dimethyl acetophenone ("Darocur 1173").

The polymerization reaction is carried out under conditions which aregenerally familiar in this field and which can be established in detailquite readily for any given set of reactants. The polymerization can becarried in the absence or presence of solvent or diluent. If thepolymerization is carried out in the absence of a diluent, the resultingpolymer can be formed, as for example by lathe cutting, into the desiredlens shape. Alternatively, and more preferably, the polymerization iscarried out in the presence of a suitable inert diluent, such as thediluents described in U.S. Pat. No. 4,680,336, the disclosure of whichis hereby incorporated herein. The preferred inert diluent is a waterdisplaceable boric acid ester, the formation and use of which aredescribed in U.S. Pat. No. 4,495,313, the disclosure of which is herebyincorporated herein. Suitable boric acid esters include those preparedby heating boric acid and one or more polyhydroxyl compounds containingthree or more hydroxy groups, such as glycerol trimethylolpropane,glucose, or mixtures of any of these with compounds having two hydroxygroups such as propylene glycol, diethylene glycol, butane diol, and/orsorbitol. The monomer mixture when combined with a solvent or diluent isplaced into a mold whose interior shape is that of a contact lens.

The monomer-initiator mixture is treated to initiate polymerization,such as by exposure to ultraviolet radiation of sufficient intensity andduration. The polymerization is allowed to proceed to completion, whichin the case of a contact lens usually requires several minutes. The lensis then removed from the mold, and hydrated in physiological saline toallow it to take its equilibrium shape and to wash out undesiredbyproducts, diluent, and the like.

Contact lenses produced in accordance with the present invention exhibithighly advantageous strength combined with a desirably high watercontent and oxygen transmissivity. These properties are apparentespecially when the inventive lenses are compared to lenses made byconventional techniques or using other reactants. In particular,equilibrating the lens in water and especially in aqueous physiologicalsaline solution (having a pH value of about 6 to about 8) converts the--COOH groups to their ionized form, such that the crosslinking agentdoes not detract from the hydrophilicity or water content of the lensand, indeed, the crosslinking agent contributes to the hydrophilicityand equilibrium water content of the lens.

The invention is described further in the following examples, which areprovided for purposes of illustration and are not intended to limit thescope of the invention for which the applicants seek patent protection.

The test methods referred to in the examples are as follows:

Test Method 1: Tensile Properties (Modulus, Elongation and TensileStrength)

The lens to be tested is cut to the desired specimen size and shape, andthe cross-sectional area is measured. The sample is then attached intothe upper grip of a constant rate of movement type of testing instrumentequipped with a load cell. The crosshead is lowered to the initial gaugelength and the sample specimen attached to the fixed grip. The sample isthen elongated at a constant rate of strain and the resultingstress-strain curve is recorded. The elongation is expressed in percentof the initial specimen dimension, and the tensile modulus and strengthat break in psi (pounds per square inch).

Test Method 2: Gravimetric Water Content

Samples for gravimetric water content measurement were prepared asfollows: A number of 20 mm diameter×3.0 mm deep cylindrical polystyrenecavities were hand filled with the formulation at 60-degrees C., andcured for approximately 20 minutes under fluorescent ultraviolet tubesin a nitrogen atmosphere. The total measured energy dose was 1.2-1.6Joules per square centimeter. The polymer/diluent discs were demoldedfrom the polystyrene cavities using a hot-plate. The discs were then cutwith a no. 7 cork bore to obtain a 9-10 mm diameter disc. Typically, thepolystyrene cavities are filled with sufficient reactive monomer mix toobtain a 1.1-1.5 mm thick disc. The diluent-swollen polymer discs werehydrated in deionized water for 48 hours at 70° C. The hydrated discswere then removed from the deionized water bath, allowed to air dry for10-15 hours, and subsequently vacuum dried (pressure<1.5 mm Hg) at 100°C. for 4 hours. The weight of each disc was taken, and the discs werethen placed in physiological saline solution at room temperature for 2days. The polymer discs were then removed from the saline solution,blotted carefully to remove surface water, and weighed again. Theequilibrium water content (EWC) is then calculated as follows:

    EWC(%)=100×(m(wet)-m(dry))/m(wet)

where m(dry) and m(wet) denote the weight of the polymer discs beforeand after hydration, respectively.

Test Method 3: Oxygen Permeability (Dk)

The oxygen permeability was measured by the method of Fatt et al.,"Measurement of Oxygen Transmissibility and Permeability of HydrogelLenses and Materials", International Contact Lens Clinic, Vol. 9/No. 2,March/April 1982, p.76. A polarographic oxygen sensor consisting of a 4mm diameter gold cathode and a silver-silver chloride ring anode areused in this method. The measured oxygen permeability is denoted by Dk,where D represents the diffusion coefficient for oxygen in the materialbeing tested and k is the solubility of oxygen in the material. Thepermeability (Dk) units are [(cm² /s)(mL O₂ /mL*mm Hg)].

EXAMPLE 1

Synthesis of Succinated Diglycidyl Bisphenol A Dimethacrylate.

A three neck, jacketed round bottom flask equipped with a Friedrichscondenser, a drying tube filled with indicating Drierite (anhydrouscalcium sulfate), a 60 mL addition funnel and a magnetic stirring bar,was flamed dry and charged with 50 g of diglycidyl bisphenol Amethacrylate (0.098 moles), 100 g of dry (% water<0.05) acetonitrile,and 20.6 g of succinic anhydride (0.206 moles). The succinic anhydridewas added to the reaction flask via a powder funnel. A catalyst solutionmade up of 22.3 g of triethylamine (0.218 moles), 1.22 g of4-dimethylamino pyridine (10 mmole) and 22 g of dry acetonitrile wascharged to the 60 mL addition funnel, and subsequently added dropwise,with rapid stirring, to the reaction flask. The addition took 5 hrs tocomplete, and was carried out at room temperature. After the additionwas finished, the reaction temperature was set at 50° C. and thereaction was allowed to proceed for 13 hrs.

The progress of the reaction was followed by infrared spectroscopy,monitoring the disappearance of the anhydride carbonyl peaks at 1770cm⁻¹ and 1850 cm⁻¹. Since excess succinic anhydride was added initially,the intensity of the peaks was followed until no further change wasnoticeable.

Product workup was carried out by first combining the crude reactionmixture with an equal volume of ethyl acetate and then washing thismixture twice with equal volumes of an aqueous 5% HCl solution, and thentwice with an equal volume of deionized water. The organic layers werethen dried over anhydrous magnesium sulfate, and the combined aqueouslayers were extracted twice with equal volumes of ethyl acetate. Theethyl acetate extracts were then dried over anhydrous magnesium sulfate.The original organic layers and the combined ethyl acetate extracts werethen filtered and the solvent removed under reduced pressure in a rotaryevaporator. The resulting light yellow clear viscous liquid was thenused as is.

EXAMPLE 2

Synthesis of Perfluoroglutaric Anhydride Derivative of DiglycidylBisphenol A Dimethacrylate.

A three neck, jacketed round bottom flask equipped with a Friedrichscondenser, a drying tube filled with indicating Drierite, a 60 mLaddition funnel and a magnetic stirring bar was flamed dry and chargedwith 27 g of diglycidyl bisphenol A dimethacrylate (0.0529 moles), 150 gof dry (% water<0.05) acetonitrile, and 23.5 g of perfluoroglutaricanhydride (0.106 moles). The reaction temperature was set at 5° C. Acatalyst solution made up of 12.1 g of triethylamine (0.120 moles),0.647 g of 4-dimethylamino pyridine (5.3 mmole) and 10 g of dryacetonitrile was charged to the 60 mL addition funnel, and subsequentlyadded dropwise, with rapid stirring, to the reaction flask. The additiontook 0.5 hr to complete. The addition funnel was then washed with anadditional 50 mL of acetonitrile. After the addition was finished, thereaction temperature was set at 50° C. and the reaction was allowed toproceed for 16 hrs (overnight).

The progress of the reaction was followed by infrared spectroscopy,monitoring the disappearance of the anhydride carbonyl peaks at 1770 and1850 cm⁻¹.

Product workup was by the same procedure employed in Example 1. Theresulting clear viscous liquid was then used as is.

EXAMPLE 3

Synthesis of Polyethylene Glycol 4500 Dimethacrylate.

A total of 100 g of dry (% water<0.05) PEG 4500 (0.022 moles) wasmelted, and poured into a three neck, 1 L two-piece jacketed roundbottom flask set up with a mechanical stirrer, a 125 mL addition funnel,and a drying tube filled with indicating Drierite. Dry isopropyl acetate(150 g) was added to the reaction flask while heating at 55° C. todissolve the PEG. Once the PEG had completely dissolved in the isopropylacetate, 12.75 g of methacrylic anhydride (0.0812 moles) was addeddropwise, with stirring, to the reaction flask. After the addition ofthe anhydride was completed, a catalyst solution of triethylamine (7.86g, 0.078 moles), 4-dimethylamino pyridine (270 mg, 2.22 mmoles) andisopropyl acetate (10 g) was charged to the addition funnel, and addeddropwise over a 1.5-2.0 hr period to the PEG/methacrylic anhydridesolution. After the catalyst solution addition was completed, the funnelwas rinsed with 50 mL of isopropyl acetate. The reaction temperature wasmaintained at 5° C. to keep the PEG 4500 in solution.

The progress of the reaction was monitored by infrared spectroscopy,following the disappearance of the anhydride carbonyl absorption at 1785cm⁻¹. In addition, aliquots of the crude reaction were analyzedchromatographically for extent of capping. The reaction was consideredto be complete whenever the amount of dicapped product exceeded 97%.Typically, this degree of conversion is arrived at by simply allowingthe reaction mix to stand overnight (14-16 hrs).

Product purification was carried out as follows. The solution containingthe product was cooled to 10° C., and the solid PEG product was pressurefiltered and rinsed with additional isopropyl acetate. Subsequently, theproduct was redissolved in acetonitrile (3:1 solvent ot PEG wt. ratio)and allowed to stir with Amberlite IRA 400-OH (3:1 wt. ratio relative tothe PEG product) at room temperature for 3 hrs. At the end of thisperiod, the Amberlite was gravity filtered and the resulting solutionwas reduced in volume in a rotary evaporator under reduced pressureuntil the PEG product began to precipitate out of solution. At thispoint, the minimum amount of acetonitrile required to redissolve the PEGproduct was added. The concentrated derivatized PEG product solution wasthen transferred to a large beaker (>1 L) and approximately 1-1.5 L ofcold ethyl ether was added to induce precipitation of the PEG product.The product was pressure filtered and rinsed with additional ethylether. The white solid product was allowed to dry overnight under anitrogen atmosphere.

EXAMPLE 4

Synthesis of IEM Capped Polyethylene Glycol 4500

A total of 100 g of dry (% water <0.05) PEG 4500 (0.022 moles) wasmelted, and poured into a three neck, 1 l two-piece jacketed roundbottom flask set up with a mechanical stirrer, a 125 mL addition funnel,and a drying tube filled with indicating DRIERITE. Dry isopropyl acetate(150 g) was added to the reaction flask while heating at 55° C. todissolve the PEG. Once the PEG had completely dissolved in the isopropylacetate, 1000 ppm of 4-methoxyhydroquinone (MEHQ) was added to thereaction flask and allowed to dissolve. A catalytic amount of stannousoctoate (100-150 mg) was added dropwise to the reaction flask. Dry airwas then bubbled into the PEG 4500 solution via a small diameterstraight tube for 20-30 minutes. A solution consisting of 6.85 g of2-isocyanatoethyl methacrylate (IEM, 0.044 moles) and 50 g of isopropylacetate was charged to the additional funnel and added dropwise, withstirring, to the reaction flask. The reaction temperature was maintainedat 55° C. to keep the PEG 4500 in solution. After the addition of theIEM solution was completed, the reaction progress was monitored byinfrared spectroscopy, following the disappearance of the isocyanateabsorption at 2270 cm⁻¹.

After the reaction was completed, product purification was carried outas follows:

The solution containing the product was cooled to 25° C., at whichtemperature it crystallizes out of solution. The solid dicapped PEGproduct was then vacuum filtered, and washed with fresh, cold isopropylacetate (100 g, T<20° C.). The product was then dried at 30° C. underreduced pressure (<3 mm Hg) for approximately 12 hours. The driedmaterial was then powdered using a mortar and pestle. Yields for thisreaction typically exceed 95% based on starting PEG 4500. The cappingefficiency is then determined chromatographically (HPLC), and is usuallyfound to be >97%.

EXAMPLES 5-10

In these examples, Glucam E-20, a 20-mole ethylene oxide methylglucoside adduct obtained commercially from Amerchol, was used as adiluent in conjunction with monomer mixtures consisting of HEMA, the PEG4500 dimethacrylate described in Example 1, and the succinateddiglycidyl bisphenol A dimethacrylate described in Example 1. Thefollowing is an illustrative preparation:

A reactive monomer mixture consisting of 0.4% by weight Darocur 1173,8.26 wt. % of the succinated diglycidyl bisphenol dimethacrylatecrosslinking agent described in Example 1, 76.3 wt. % HEMA, and 15.0 wt.% of the PEG 4500 dimethacrylate crosslinker described in Example 3 wasmixed with enough Glucam E-20 to make up a 48% reactive monomer/52%diluent mixture.

After thoroughly mixing this formulation at 65° C., it was transferredto contact lens molds. The filled molds were exposed to UV light(wavelength 300-380 nm, dose=1.2-1.6 Joules/cm²) for 20 minutes atapproximately 65° C. The molds were then separated, and placed inphysiological saline for 3 hours at 70 C. to remove the inert diluentand any unreacted monomers. After this initial hydration period, thelenses were allowed to equilibrate to room temperature in a fresh bathof physiological saline. The lenses were then tested according to testmethods 1 and 3, and the EWC of each material was determined accordingto test method 2.

Table 1 displays the proportion of the various monomers and the resultsof the tests made in accordance with test methods 1-3 for the productsformed in Examples 5-10.

EXAMPLES 11-16

In these examples, Glucam E-20 was used as a diluent in conjunction withmonomer mixtures consisting of HEMA, the PEG 4500/IEM adduct describedin Example 4, Darocur 1173, and the succinated diglycidyl bisphenol Adimethacrylate crosslinker described in Example 1. The following is anillustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 8.26wt. % of the succinated diglycidyl bisphenol A crosslinker described inExample 1, 76.3 wt. % HEMA, and 15.0 wt. % of the IEM dicapped PEG 4500dimethacrylate crosslinker described in Example 4 was mixed with enoughGlucam E-20 to make up a 48 wt. % reactive monomer/52 wt. % diluentmixture. After thoroughly mixing this formulation at 65° C., it wastransferred to lens molds and treated by the same steps employed inExamples 5-10. Table 2 displays the proportion of the various monomersand the results of the tests made in accordance with test methods 1-3for the products formed in Examples 11-16.

EXAMPLES 17-21

These examples, of lenses prepared using reactants other than thecrosslinking agent of formula (1), are useful to show that lensesprepared in accordance with the present invention including acrosslinking agent of formula (1) exhibit consistently superiorproperties.

In these examples, a mixture consisting of 50 wt. % Glucam E-20 and 50wt. % Photonol 7025, an 8-mole ethoxylated bisphenol A diol obtainedfrom Henkel, was used as a diluent with monomer blends of HEMA, the PEG4500/IEM adduct described in Example 4, Darocur 1173, and diglycidylbisphenol A dimethacrylate (obtained from PolySciences). The followingis an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 5.1 wt.% of commercially obtained diglycidyl bisphenol A dimethacrylate, 79.5wt. % HEMA, and 15.0 wt. % of the PEG 4500/IEM adduct described inExample 4 was mixed with enough 50:50 Glucam E-20/Photonol 7025 to makeup a 50 wt. % reactive monomer/50 wt. % diluent mixture. Afterthoroughly mixing this formulation at 65° C. and transferring it tocontact lens molds it was treated by the steps used in Examples 5-10.Table 3 displays the proportion of the various monomers and the resultsof the tests made in accordance with test methods 1-3 for the productsformed in Examples 17-21.

EXAMPLES 22-26

In these examples, a 50:50 (wt.) mixture of Glucam E-20 and Photonol7025 was used as a diluent with monomer blends of HEMA, 15.0 wt. % ofthe adduct described in Example 4, Darocur 1173, and the succinateddiglycidyl bisphenol A dimethacrylate described in Example 1. Thefollowing is an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 7.1 wt.% of the succinated diglycidyl bisphenol A dimethacrylate crosslinkerdescribed in Example 1, 77.5 wt. % HEMA, and 15.0 wt. % of the IEMdicapped PEG 4500 dimethacrylate crosslinker described in Example 4 wasmixed with enough of the 50:50 Glucam E-20/Photonol 7025 diluent to makeup a 50 wt. % reactive monomer/50 wt. % diluent mixture, which wasthoroughly mixed at 65° C., transferred to contact lens molds, andtreated using the steps employed in Examples 5-10. Table 4 displays theproportion of the various monomers and the results of the tests made inaccordance with test methods 1-3 for the products formed in Examples22-26.

EXAMPLES 27-31

In these examples, a 50:50 (wt.) mixture of Glucam E-20 and Photonol7025 was used as a diluent with monomer blends of HEMA, the PEG 4500/IEMadduct described in Example 4, Darocur 1173, and the perfluoroglutaricanhydride/diglycidyl bisphenol A dimethacrylate derivative described inExample 2. The following is an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 9.6 wt.% of the perfluoroglutaric anhydride/diglycidyl bisphenol Adimethacrylate derivative described in Example 2, 75 wt. % HEMA, and15.0 wt. % of the IEM dicapped PEG 4500 dimethacrylate crosslinkerdescribed in Example 4 was mixed with enough of the 50:50 GlucamE20/Photonol 7025 diluent to make up a 50 wt. % reactive monomer/50 wt.% diluent mixture. After thoroughly mixing the mixture at 65° C., themixture was transferred to contact lens molds and treated using thesteps employed in Examples 5-10. Table 5 displays the proportion of thevarious monomers and the results of the tests made in accordance withtest methods 1-3 for the products formed in Examples 27-31.

EXAMPLES 32-37

These are additional examples of lenses made not with a crosslinkingagent of formula (1) used in the present invention, to demonstrate thatthe lenses of the present invention exhibit superior properties.

In these examples, a 50:50 (wt.) mixture of Glucam E-20 and Photonol7025 was used as a diluent with monomer blends of HEMA, the PEG 4500/IEMadduct described in Example 4, Darocur 1173, and diglycidyl bisphenol Adimethacrylate (obtained from Polysciences). The following is anillustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 5.1 wt.% of commercially obtained diglycidyl bisphenol A dimethacrylate, 84.5wt. % HEMA, and 10.0 wt. % of the PEG 4500/IEM adduct described inExample 4 was mixed with enough 50:50 Glucal E-20/Photonol 7025 to makea 60 wt. % reactive monomer/40 wt. % diluent formulation. Afterthoroughly mixing this formulation at 65° C., it was transferred tocontact lens molds and treated by the steps used in Examples 5-10. Table6 displays the proportion of the various monomers and the results of thetests made in accordance with test methods 1-3 for the products formedin Examples 32-37.

EXAMPLES 38-43

In these examples, a 50:50 (wt.) mixture of Glucam E-20 and Photonol7025 was used as a diluent with monomer blends of HEMA, the PEG 4500/IEMadduct described in Example 4, Darocur 1173, and the succinateddiglycidyl bisphenol A dimethacrylate described in Example 1. Thefollowing is an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 7.1 wt.% of the succinated diglycidyl bisphenol A crosslinker described inExample 1, 82.5 wt. % HEMA, and 10.0 wt. % of the IEM dicapped PEG 4500dimethacrylate crosslinker described in Example 4 was mixed with enoughof the 50:50 Glucam E-20/Photonol 7025 diluent to make up a 60 wt. %reactive monomer/40 wt. % diluent formulation. After thoroughly mixingthis formulation at 65° C., it was transferred to contact lens molds andtreated by the steps used in Examples 5-10. Table 7 displays theproportion of the various monomers and the results of the tests made inaccordance with test methods 1-3 for the products formed in Examples38-43.

EXAMPLES 44-49

In these examples, a 50:50 (wt.) mixture of Glucam E-20 and Photonol7025 was used as a diluent with monomer blends of HEMA, the PEG 4500/IEMadduct described in Example 4, Darocur 1173, and the perfluoroglutaricanhydride/diglycidyl bisphenol A dimethacrylate derivative described inExample 2. The following is an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 9.6 wt.% of the perfluoroglutaric anhydride/diglycidyl bisphenol Adimethacrylate derivative described in Example 2, 80.0 wt. % HEMA, and10.0 wt. % of the IEM dicapped PEG 4500 dimethacrylate crosslinkerdescribed in Example 4 was mixed with enough of the 50:50 mixture ofGlucam E-20 and Photonol 7025 to make up a 60 wt. % reactive monomer/40wt. % diluent formulation. After thoroughly mixing this formulation at65° C., it was transferred to contact lens molds and treated by thesteps used in Examples 5-10. Table 8 displays the proportion of thevarious monomers and the results of the tests made in accordance withtest methods 1-3 for the products formed in Examples 44-49.

EXAMPLES 50-54

These are additional examples of lenses made not using a crosslinkingagent of formula (1), to help show that the lenses of the presentinvention exhibit superior properties.

In these examples, Photonol 7025 was used as a diluent with monomerblends of HEMA, Darocur 1173, methacrylic acid, and diglycidyl bisphenolA dimethacrylate (obtained from Polysciences). The following is anillustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 3.7 wt.% of commercially obtained diglycidyl bisphenol A dimethacrylate, 93.9wt. % HEMA, and 2.0 wt. % methacrylic acid was mixed with enoughPhotonol 7025 to make up a 48 wt. % reactive monomer/52 wt. % diluentformulation. After thoroughly mixing this formulation at 25° C., it wasdegassed at 40 mm Hg for 25 min in a rotary evaporator. The formulationwas then transferred to contact lens molds and treated by the steps usedin Examples 5-10 except that the exposure to UV light was carried out ata temperature of 55° C. Table 9 displays the proportion of the variousmonomers and the results of the tests made in accordance with testmethods 1-3 for the products formed in Examples 50-54.

EXAMPLES 55-59

In these examples, Photonol 7025 was used as a diluent with monomerblends of HEMA, Darocur 1173, methacrylic acid, and the succinateddiglycidyl bisphenol A dimethacrylate described in Example 1. Thefollowing is an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 3.7 wt.% of the succinated bisphenol A dimethacrylate described in Example 1,93.9 wt. % HEMA, and 2.0 wt. % methacrylic acid was mixed with enoughPhotonol 7025 to make up a 48 wt. % reactive monomer/52 wt. % diluentformulation. After thoroughly mixing this formulation at 25° C., it wastransferred to contact lens molds and treated by the steps used inExamples 50-54. Table 10 displays the proportion of the various monomersand the results of the tests made in accordance with test methods 1-3for the products formed in Examples 55-59. By comparing the data inTable 10 with the data in Tables 9 and 11, wherein all the lenses wereof HEMA and methacrylic acid but only those of Table 10 employed thecrosslinking agent of the present invention, it can be seen that thelenses of the present invention exhibit superior properties.

Examples 60-64

These are additional examples of lenses not made using a crosslinkingagent according to the present invention, to help show that the lensesof the present invention exhibit superior properties. In these examples,Photonol was used as a diluent with monomer blends of HEMA, Darocur1173, the IEM dicapped PEG 4500 dimethacrylate described in Example 4,and ethylene glycol dimethacrylate. The following is an illustrativepreparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 2.6 wt.% of ethylene glycol dimethacrylate, 87.0 wt. % HEMA and 10.0 wt. % ofthe IEM dicapped PEG 4500 dimethacrylate described in Example 4 wasmixed with enough Photonol 7025 to make up a 48 wt. % reactivemonomer/52 wt. % diluent formulation. After thoroughly mixing thisformulation at 25° C., it was degassed at 40 mm Hg for 25 min in arotary evaporator and was then transferred to contact lens molds andtreated by the steps used in Examples 50-54. Table 11 displays theproportion of the various monomers and the results of the tests made inaccordance with test methods 1-3 for the products formed in Examples60-64.

EXAMPLE 65

Synthesis of 4,4'-(Hexafluoroisopropylidine)di-phthalic anhydride/HEMAAdduct.

To a flask equipped and prepared as in Example 1 were charged 40 g of4,4'-(hexafluoropropylidine)-di-phthalic anhydride (0.09 moles), 320 gof dry (% water<0.05) tetrahydrofuran (THF) and 23.4 g of HEMA (0.18moles). A catalyst solution of 18.2 g of triethylamine (0.18 moles), 1.1g of 4-dimethylamino pyridine (9 mmoles) and 20 g of dry THF was chargedto the 60 mL addition funnel, and subsequently added dropwise, withrapid stirring, to the reaction flask. The addition took 3 hrs tocomplete, and was carried out at room temperature. The reaction was thenallowed to proceed for 12-16 hrs (overnight) at 25° C.

The progress of the reaction was followed by infrared spectroscopy,monitoring the disappearance of the anhydride carbonyl peaks at 1770cm⁻¹ and 1850 cm⁻¹.

Product workup employed the procedure used in Example 1. A total of 34.9g of a light yellow clear viscous liquid (55.1% yield) was obtained andused as is.

EXAMPLES 66-71

In these examples, a 50:50 (wt.) mixture of Glucam E-20 and Photonol7025 was used as a diluent with monomer blends of HEMA, Darocur 1173,the IEM dicapped PEG 4500 dimethacrylate described in Example 4, and thefluoroanhydride/HEMA crosslinker described in Example 65. The followingis an illustrative preparation:

A reactive monomer mixture consisting of 0.4 wt. % Darocur 1173, 2.8 wt.% of the fluorocrosslinker described in Example 65, 86.8 wt. % HEMA, and10.0 wt. % of the IEM dicapped PEG 4500 dimethacrylate described inExample 4 was mixed with enough of the 50:50 Glucam E-20/Photonol 7025mixture to make up a 60 wt. % reactive monomer/40 wt. % diluentformulation. After thoroughly mixing this formulation at 25° C., it wasdegassed at 40 mm Hg for 25 min in a rotary evaporator and was thentransferred to contact lens molds and treated by the steps used inExamples 50-54. Table 12 displays the proportion of the various monomersand the results of the tests made in accordance with test methods 1-3for the products formed in Examples 66-71.

The following Tables demonstrate that contact lenses formed using acrosslinking agent of formula (1), in accordance with the presentinvention, possess physical properties that are superior compared evento contact lenses made otherwise from the same materials and using thesame diluents and proportions of diluents.

    ______________________________________                                        ABREVIATIONS GUIDE                                                            Abrevia-                                                                      tion    Description                                                           ______________________________________                                        HEMA    Hydroxyethyl Methacrylate                                             MAA     Methacrylic Acid                                                      EGDMA   Ethylene Glycol Dimethacrylate                                        MAnh    Methacrylic Anhydride                                                 IEM     Isocyanatoethyl Methacrylate                                          DGBPA   Diglycidyl Bisphenol A Dimethacrylate                                 SuccBPA Succinated Diglycidyl Bisphenol A Dimethacrylate                      FGABPA  Fluoroglutaric Anhydride/DGBPA Adduct (ex 65)                         IEM DC  IEM Dicapped Polyethylene Glycol 4500 (ex 4)                          PEG 450(                                                                      DC PEG  MAnh Dlcapped Polyethylene Glycol 4500 (ex 3)                         4500                                                                          ______________________________________                                    

                                      TABLE 1                                     __________________________________________________________________________    Examples 5-10.                                                                          Example 5                                                                           Example 6                                                                           Example 7                                                                           Example 8                                                                           Example 9                                                                           Example 10                            __________________________________________________________________________    Composition (%):                                                              HEMA      86.3  81.3  76.3  66.3  56.3  48.3                                  SuccBPA (ex 1)                                                                          8.3   8.3   8.3   8.3   8.3   8.3                                   PEG4500DC (ex 4)                                                                        5.0   10.0  15.0  25.0  35.0  43.0                                  DC 1173   0.4   0.4   0.4   0.4   0.4   0.4                                   Diluent (%):                                                                  GLUCAM E-20                                                                             100   100   100   100   100   100                                   Mon/Dil Ratio                                                                           48:52 48:52 48:52 48:52 48:52 48:52                                 Properties:                                                                   Modulus (psi)                                                                           97    93    99    98    104   115                                   % Elongation                                                                            110   142   137   141   143   126                                   Tensile Strength (ps                                                                    62    81    85    93    99    92                                    EWC (%)   49.1  51.7  55.0  60.0  61.7  63.9                                  Dk        17    18    22    29    32    35                                    __________________________________________________________________________

                                      TABLE 2                                     __________________________________________________________________________    Examples 11-16.                                                                         Example 11                                                                          Example 12                                                                          Example 13                                                                          Example 14                                                                          Example 15                                                                          Example 16                            __________________________________________________________________________    Composition (%):                                                              HEMA      86.3  81.3  76.3  66.3  56.3  48.3                                  SuccBPA (ex 1)                                                                          8.3   8.3   8.3   8.3   8.3   8.3                                   PEG4500DC (ex 3)                                                                        5.0   10.0  15.0  25.0  35.0  43.0                                  DC 1173   0.4   0.4   0.4   0.4   0.4   0.4                                   Diluent (%):                                                                  GLUCAM E-20                                                                             100   100   100   100   100   100                                   Mon/Dil Ratio                                                                           48:52 48:52 48:52 48:52 48:52 48:52                                 Properties:                                                                   Modulus (psi)                                                                           106   106   101   111   114   114                                   % Elongation                                                                            103   107   134   156   173   165                                   Tensile Strength (ps                                                                    65    70    86    115   118   112                                   EWC (%)   49.1  51.1  53.3  57.3  61.3  63.8                                  Dk        16    20    22    22    24    30                                    __________________________________________________________________________

                                      TABLE 3                                     __________________________________________________________________________    Examples 17-21.                                                                          Example 17                                                                          Example 18                                                                          Example 19                                                                          Example 20                                                                          Example 21                                 __________________________________________________________________________    Composition (%):                                                              HEMA       82.0  80.5  79.5  78.2  76.9                                       DGBPA      2.6   4.1   5.1   6.4   7.7                                        PEG4500DC (ex 3)                                                                         15.0  15.0  15.0  15.0  15.0                                       DC 1173    0.4   0.4   0.4   0.4   0.4                                        Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50                                         Photonol 7025                                                                            50    50    50    50    50                                         Mon/Dil Ratio                                                                            50:50 50:50 50:50 50:50 50:50                                      Properties:                                                                   Modulus (psi)                                                                            71    91    108   125   137                                        % Elongation                                                                             123   126   177   122   138                                        Tensile Strength (psi)                                                                   55    72    109   97    120                                        EWC (%)    54.5  51.7  50.6  48.8  47.2                                       Dk         17    16    14    13    11                                         __________________________________________________________________________

                                      TABLE 4                                     __________________________________________________________________________    Examples 22-26.                                                                          Example 22                                                                          Example 23                                                                          Example 24                                                                          Example 25                                                                          Example 26                                 __________________________________________________________________________    Composition (%):                                                              HEMA       81.0  78.9  77.5  75.7  73.9                                       SuccBPA (ex 1)                                                                           3.6   5.7   7.1   8.9   10.7                                       PEG4500DC (ex 4)                                                                         15.0  15.0  15.0  15.0  15.0                                       DC 1173    0.4   0.4   0.4   0.4   0.4                                        Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50                                         Photonol 7025                                                                            50    50    50    50    50                                         Mon/Dil Ratio                                                                            50:50 50:50 50:50 50:50 50:50                                      Properties:                                                                   Modulus (psi)                                                                            63    69    81    105   130                                        % Elongation                                                                             120   169   169   95    125                                        Tensile Strength (psi)                                                                   45    78    94    58    93                                         EWC (%)    57.5  56.9  56.8  56.1  56.1                                       Dk         20    21    21    19    19                                         __________________________________________________________________________

                                      TABLE 5                                     __________________________________________________________________________    Examples 27-31.                                                                          Example 27                                                                          Example 28                                                                          Example 29                                                                          Example 30                                                                          Example 31                                 __________________________________________________________________________    Composition (%):                                                              HEMA       79.8  76.9  75.0  72.6  70.3                                       FGABPA (ex 2)                                                                            4.8   7.7   9.6   12.0  14.3                                       PEG4500DC (ex 4)                                                                         15.0  15.0  15.0  15.0  15.0                                       DC 1173    0.4   0.4   0.4   0.4   0.4                                        Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50                                         Photonol 7025                                                                            50    50    50    50    50                                         Mon/Dil Ratio                                                                            50:50 50:50 50:50 50:50 50:50                                      Properties:                                                                   Modulus (psi)                                                                            50    63    58    74    68                                         % Elongation                                                                             175   202   194   210   157                                        Tensile Strength (psi)                                                                   46    66    58    84    58                                         EWC (%)    57.8  56.8  56.6  56.4  56.1                                       Dk         19    20    20    15    20                                         __________________________________________________________________________

                                      TABLE 6                                     __________________________________________________________________________    Examples 32-37.                                                                          Example 32                                                                          Example 33                                                                          Example 34                                                                          Example 35                                                                          Example 36                                                                          Example 37                           __________________________________________________________________________    Composition (%):                                                              HEMA       88.6  87.6  85.5  84.5  81.9  76.8                                 DGBPA      1.0   2.0   4.1   5.1   7.7   12.8                                 PEG4500DC (ex 4)                                                                         10.0  10.0  10.0  10.0  10.0  10.0                                 DC 1173    0.4   0.4   0.4   0.4   0.4   0.4                                  Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50    50                                   Photonol 7025                                                                            50    50    50    50    50    50                                   Mon/Dil Ratio                                                                            60:40 60:40 60:40 60:40 60:40 60:40                                Properties:                                                                   Modulus (psi)                                                                            38    56    82    93    138   311                                  % Elongation                                                                             173   174   160   148   155   147                                  Tensile Strength (psi)                                                                   40    50    74    76    117   152                                  EWC (%)    45.9  45.0  42.6  42.9  40.2  35.7                                 Dk         15    16    14    12    11    8.2                                  __________________________________________________________________________

                                      TABLE 7                                     __________________________________________________________________________    Examples 38-43.                                                                          Example 38                                                                          Example 39                                                                          Example 40                                                                          Example 41                                                                          Example 42                                                                          Example 43                           __________________________________________________________________________    Composition (%):                                                              HEMA       88.2  86.8  83.9  82.5  78.9  71.8                                 SuccBPA (ex 1)                                                                           1.4   2.8   5.7   7.1   10.7  17.8                                 PEG4500DC (ex 3)                                                                         10.0  10.0  10.0  10.0  10.0  10.0                                 DC 1173    0.4   0.4   0.4   0.4   0.4   0.4                                  Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50    50                                   Photonol 7025                                                                            50    50    50    50    50    50                                   Mon/Dil Ratio                                                                            40:60 40:60 40:60 40:60 40:60 40:60                                Properties:                                                                   Modulus (psi)                                                                            41    49    68    76    106   175                                  % Elongation                                                                             232   215   165   108   112   83                                   Tensile Strength (psi)                                                                   46    53    62    47    69    87                                   EWC (%)    48.6  49.7  51.4  53.7  55.0  55.5                                 Dk         18    20    21    23    24    24                                   __________________________________________________________________________

                                      TABLE 8                                     __________________________________________________________________________    Examples 44-49.                                                                          Example 44                                                                          Example 45                                                                          Example 46                                                                          Example 47                                                                          Example 48                                                                          Example 49                           __________________________________________________________________________    Composition (%):                                                              HEMA       87.7  85.8  82.0  80.1  75.3  65.7                                 FGABPA (ex 2)                                                                            1.9   3.8   7.6   9.5   14.3  23.9                                 PEG4500DC (ex 4)                                                                         10.0  10.0  10.0  10.0  10.0  10.0                                 DC 1173    0.4   0.4   0.4   0.4   0.4   0.4                                  Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50    50                                   Photonol 7025                                                                            50    50    50    50    50    50                                   Mon/Dil Ratio                                                                            60:40 60:40 60:40 60:40 60:40 60:40                                Properties:                                                                   Modulus (psi)                                                                            37    42    52    56    67    102                                  % Elongation                                                                             232   179   161   178   176   167                                  Tensile Strength (psi)                                                                   38    35    42    50    61    90                                   EWC (%)    46.5  45.3  41.1  44.9  43.9  41.8                                 Dk         17    16    15    14    15    13                                   __________________________________________________________________________

                                      TABLE 9                                     __________________________________________________________________________    Examples 50-54.                                                                          Example 50                                                                          Example 51                                                                          Example 52                                                                          Example 53                                                                          Example 54                                 __________________________________________________________________________    Composition (%):                                                              HEMA       95.6  94.5  93.5  92.5  89.9                                       DGBPA      2.0   3.1   4.1   5.1   7.7                                        MAA        2.0   2.0   2.0   2.0   2.0                                        DC 1173    0.4   0.4   0.4   0.4   0.4                                        Diluent (%):                                                                  Photonol 7025                                                                            100   100   100   100   100                                        Mon/Dil Ratio                                                                            48:52 48:52 48:52 48:52 48:52                                      Properties:                                                                   Modulus (psi)                                                                            42    49    61    69    89                                         % Elongation                                                                             115   98    78    80    69                                         Tensile Strength (psi)                                                                   36    39    42    50    63                                         EWC (%)    47    45    42    43    39                                         __________________________________________________________________________

                                      TABLE 10                                    __________________________________________________________________________    Examples 55-59.                                                                          Example 55                                                                          Example 56                                                                          Example 57                                                                          Example 58                                                                          Example 59                                 __________________________________________________________________________    Composition (%):                                                              HEMA       94.8  93.3  91.9  90.5  86.9                                       SuccBPA (ex 1)                                                                           2.8   4.3   5.7   7.1   10.7                                       MAA        2.0   2.0   2.0   2.0   2.0                                        DC 1173    0.4   0.4   0.4   0.4   0.4                                        Diluent (%):                                                                  Photonol 7025                                                                            100   100   100   100   100                                        Mon/Dil Ratio                                                                            48:52 48:52 48:52 48:52 48:52                                      Properties:                                                                   Modulus (psi)                                                                            39    45    57    64    80                                         % Elongation                                                                             161   96    77    60    46                                         Tensile Strength (psi)                                                                   46    37    39    40    41                                         EWC (%)    51    50    52    53    53                                         __________________________________________________________________________

                                      TABLE 11                                    __________________________________________________________________________    Examples 60-64.                                                                          Example 60                                                                          Example 61                                                                          Example 62                                                                          Example 63                                                                          Example 64                                 __________________________________________________________________________    Composition (%):                                                              HEMA       88.9  88.3  87.0  86.3  84.6                                       PEG 4500DMA (ex 4)                                                                       10.0  10.0  10.0  10.0  10.0                                       EGDMA      0.7   1.3   2.6   3.3   5.0                                        DC 1173    0.4   0.4   0.4   0.4   0.4                                        Diluent (%):                                                                  Photonol 7025                                                                            100   100   100   100   100                                        Mon/Dil Ratio                                                                            48:52 48:52 48:52 48:52 48:52                                      Properties:                                                                   Modulus (psi)                                                                            85    102   152   173   280                                        % Elongation                                                                             184   125   105   112   94                                         EWC (%)    48.9  47.6  45.9  45.1  43.3                                       __________________________________________________________________________

                                      TABLE 12                                    __________________________________________________________________________    Examples 66-71.                                                                          Example 66                                                                          Example 67                                                                          Example 68                                                                          Example 69                                                                          Example 70                                                                          Example 71                           __________________________________________________________________________    Composition (%):                                                              HEMA       88.2  86.8  83.9  82.6  79.0  72.2                                 PEG 4500DMA (ex 4)                                                                       10.0  10.0  10.0  10.0  10.0  10.0                                 HFBPA (ex 65)                                                                            1.4   2.8   5.7   7.0   10.6  17.4                                 DC 1173    0.4   0.4   0.4   0.4   0.4   0.4                                  Diluent (%):                                                                  GLUCAM E-20                                                                              50    50    50    50    50    50                                   Photonol 7025                                                                            50    50    50    50    50    50                                   Mon/Dil Ratio                                                                            60:40 60:40 60:40 60:40 60:40 60:40                                Properties:                                                                   Modulus (psi)                                                                            54    64    71    88    100   134                                  % Elongation                                                                             196   157   129   102   113   77                                   EWC (%)    51.8  52.5  55.3  55.9  58.4  61.8                                 Dk         15.0  15.4  18.7  20.4  22.4  29.4                                 __________________________________________________________________________     HFBPADMA = Hexafluoro bisphenol A dimethacrylate (example 65).           

What is claimed is:
 1. A hydrophilic contact lens formed bycopolymerizing a polymerizable mixture comprising at least onehydrophilic monomer and further comprising at least one crosslinkingagent of formula (1):

    A--X--(O--(C(O)).sub.i --R--(C(O)).sub.i --O--X).sub.n --A (1)

wherein n is 1 to 6; i is independently in each occurrence 0 or 1; R isa divalent bridge containing at least one saturated or unsaturatedcyclic or bicyclic moiety; X is a linear divalent alkyl bridgecontaining 2 to 12 carbon atoms optionally substituted with at least oneside chain containing a --OC(O)-- linkage and a total of up to 12 carbonatoms, which side chain is optionally substituted with fluorine andoptionally contains a phenyl ring that can optionally be substitutedwith alkyl containing 1 to 6 carbon atoms; and A is acrylate,methacrylate, vinylbenzoyloxy, or vinylphenoxy, from the terminal oxygenof which is optionally pendant a polyalkoxy group containing 1 to 10ethoxy or propoxy units; provided that said crosslinking agent issubstituted with at least one --COOH group on R or X.
 2. A contact lensaccording to claim 1 wherein said polymerizable mixture comprises HEMA.3. A contact lens according to claim 2 wherein n is 1 or
 2. 4. A contactlens according to claim 3 wherein R has the formula --Ph--Z--Ph whereineach --Ph-- denotes a phenyl ring which is optionally substituted withone or two alkyl groups containing 1 to 6 carbon atoms, and Z denotes achemical bond, --O--, --SO₂ --, or --C(Y)₂ -- wherein Y is hydrogen oralkyl containing 1 to 6 carbon atoms which is optionally substitutedwith fluorine.
 5. A contact lens according to claim 4 wherein A isacrylate or methacrylate.
 6. A contact lens according to claim 5 whereinsaid crosslinking agent of formula (1) is substituted on R, X or bothwith at least two --COOH groups.
 7. A contact lens according to claim 6where each X is substituted with a --COOH group.
 8. A contact lensaccording to claim 7 wherein each X is a linear alkyl group containing 2or 3 carbon atoms which is substituted with a side chain that containsup to 12 carbon atoms, contains a --OC(O)-- linkage, optionally containsa phenyl ring and is optionally substituted with fluorine.
 9. A contactlens according to claim 8 wherein each X is a linear group containing 2or 3 carbon atoms which is substituted with --OC(O)--L--COOH wherein Lis --CH₂ CH₂ --, --CH(CH₃)CH₂ --, --CH═CH--, --CF₂ CF₂ --, --CF₂ CF₂ CF₂--, --CH₂ CH₂ CH₂ --, --CH(═CH₂)CH₂, or --C₆ H₄ --.
 10. A contact lensaccording to claim 1 wherein n is 1 or
 2. 11. A contact lens accordingto claim 1 wherein R has the formula --Ph--Z--Ph-- wherein each --Ph--denotes a phenyl ring which is optionally substituted with one or twoalkyl groups containing 1 to 6 carbon atoms, and Z denotes a chemicalbond, --O--, --SO₂ --, or --C(Y)₂ -- wherein Y is hydrogen or alkylcontaining 1 to 6 carbon atoms which is optionally substituted withfluorine.
 12. A contact lens according to claim 1 wherein A is acrylateor methacrylate.
 13. A contact lens according to claim 1 wherein saidcrosslinking agent of formula (1) is substituted on R, X or both with atleast two --COOH groups.
 14. A contact lens according to claim 1 whereeach X is substituted with a --COOH group.
 15. A contact lens accordingto claim 1 wherein each X is a linear alkyl group containing 2 or 3carbon atoms which is substituted with a side chain that contains up to12 carbon atoms, contains a --OC(O)-- linkage, optionally contains aphenyl ring and is optionally substituted with fluorine.
 16. A contactlens according to claim 1 wherein each X is a linear group containing 2or 3 carbon atoms which is substituted with --OC(O)--L--COOH wherein Lis --CH₂ CH₂ --, --CH(CH₃)CH₂ --, --CH═CH--, --CF₂ CF₂ --, --CF₂ CF₂ CF₂--, --CH₂ CH₂ CH₂ --, --CH(═CH₂)CH₂, or --C₆ H₄.
 17. A contact lensaccording to claim 3 wherein R is phenyl or a fused two-ring homocyclicmoiety and is optionally substituted with alkyl that contains 1 to 6carbon atoms and is optionally substituted with fluorine.
 18. A contactlens according to claim 16 wherein A is acrylate or methacrylate.
 19. Acontact lens according to claim 17 wherein said crosslinking agent offormula (1) is substituted on R, X or both with at least two --COOHgroups.
 20. A contact lens according to claim 18 wherein R issubstituted with at least two --COOH groups.
 21. A contact lensaccording to claim 19 wherein each X is a linear alkyl group containing2 or 3 carbon atoms.
 22. A contact lens according to claim 1 wherein Ris phenyl or a fused two-ring homocyclic moiety and is optionallysubstituted with alkyl that contains 1 to 6 carbon atoms and isoptionally substituted with fluorine.
 23. A contact lens according toclaim 1 wherein R is substituted with at least two --COOH groups.
 24. Acontact lens according to claim 1 wherein each X is a linear alkyl groupcontaining 2 or 3 carbon atoms.